Most human inherited diseases and cancers are known to be caused by mutations in nuclear genes. In general, a mutation is considered to be particular polymorphic variants at a genetic locus. The mutation can be a single nucleotide difference, often referred to as a point mutation. At the cellular and tissue level, polymorphisms at a specific genetic locus may give rise to significantly altered cellular behavior. However, because even relatively small cell or tissue samples can contain millions or billions of DNA molecules containing the particular genetic locus, a representation of the range and frequencies of polymorphic variants at a genetic locus, requires detecting alleles that are potentially present at a very low frequency. In most cases, the detection of the presence of rare mutations from a biological sample presents tremendous challenges due to the simultaneous presence of a vast excess of wild-type DNA.
Thus there exists a need in the art for a method to selectively and accurately enrich low-copy mutant DNA such that their presence can be detectable following the performance of amplification reactions such as PCR.